title: Methylating agents as trypanocides.
abstract: Methylating agents, such as streptozotocin, procarbazine, N-methyl-N-nitrosourea, dimethyl sulfate, 1,2-dimethylhydrazine, and a series of 1,2-bis(sulfonyl)-1-methylhydrazines synthesized in this laboratory, were evaluated and shown to be therapeutically active against murine models of African trypanosomiasis. At high dose levels, methylating agents halted trypanosome proliferation and transformed cells into bizarre forms containing multiple nuclei and kinetoplasts. These cells disappeared from the bloodstream of mice bearing these organisms in 48-72 h. When administered at repetitive low doses, methylating agents induced the entire population of trypanosomes to differentiate into biochemically distinct short-stumpy forms in a synchronous manner. These results suggest that methylating agents may be used as biochemical tools in the study of trypanosome differentiation.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: P G
authors.initials: PG
authors.lastname: Penketh
authors.forename: K
authors.initials: K
authors.lastname: Shyam
authors.forename: A A
authors.initials: AA
authors.lastname: Divo
authors.forename: C L
authors.initials: CL
authors.lastname: Patton
authors.forename: A C
authors.initials: AC
authors.lastname: Sartorelli
mesh_terms: D000477:Alkylating Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D000818:Animals; D008745:Methylation; D051379:Mice; D014344:Trypanocidal Agents / Q000138:chemical synthesis*; D014346:Trypanosoma brucei brucei; D014352:Trypanosomiasis / Q000188:drug therapy*
chemical_list: D000477:Alkylating Agents; D014344:Trypanocidal Agents